Safety of Adalimumab and Predictors of Adverse Events in 1693 Japanese Patients with Crohn’s Disease

Abstract

Background and Aims:Data from an all-cases post-marketing study were used to evaluate the safety and effectiveness of adalimumab in Japanese patients with Crohn’s disease [CD].Methods:Patients received adalimumab for 24 weeks. Data from all patients [n = 1693] were used for the safety assessment. Data from patients with CD activity index [CDAI] ≥ 150 at baseline were used for the effectiveness assessment.Results:The most frequent serious adverse drug reaction [ADR] was infection and infestations [6.6 events/100 patient-years]. The risk of serious infections increased in patients who had a history of malignancy and those with concomitant corticosteroid use. Of 415 patients who had switched from another anti-tumour necrosis factor alpha [TNFα] agent to adalimumab due to ADRs, 7.2% discontinued due to ADRs to adalimumab. Ten of 13 patients with a history of tuberculosis [TB] received prophylactic medication, and none developed TB. TB developed in one patient with no history of TB or anti-TB prophylaxis. Remission rates were 41.3% and 32.4% at 4 and 24 weeks, respectively. Remission rates did not differ between patients with and without concomitant use of immunomodulators. Predictive variables for increased effectiveness were CDAI ≤ 220 and disease duration of ≤ 2 years. Perianal lesions and loss of response to previous anti-TNFα agents affected effectiveness.Conclusions:The most frequent serious ADR was infection. Adalimumab significantly reduced disease activity, without any unexpected ADRs. Development of active TB during adalimumab therapy can be prevented through TB screening and prophylaxis. In patients who switched from another anti-TNFα agent to adalimumab due to ADRs, adalimumab was well tolerated.

Systematic review and meta‐analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn’s disease

“…In two other post hoc analyses, the CR rates in early versus late treatment groups were 56% vs 58% (n = 945, <2 vs 2‐5 years at 20 weeks, CR was defined as HBI ≤4) and 46% vs 28% (n = 777, <2 vs 2‐≤5 years at 26 weeks) . Two large observational studies reported similar trends in higher remission rates in early versus late/conventional treatment group …”

“…Eight studies reported higher clinical remission rates (Table 3) with early treatment (38%‐81.5%) versus late/conventional treatment (14%‐80%) . In an RCT, the CR rates for early versus late/conventional were 60.6% vs 35.9% ( P = .0062) .…”

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease

“…In particular, the antitumor necrosis factor‐alpha (TNF‐α) agents infliximab (IFX), adalimumab (ADA), and certolizumab pegol (not approved in Japan) have altered the treatment strategy for patients with CD. Treatment with anti‐TNF‐α agents, however, may cause difficulties, such as primary nonresponse, secondary loss of response (LOR) after achieving remission, and related adverse events, including paradoxical psoriasis . LOR occurs in ~20% of CD patients treated with anti‐TNF‐α agents who achieved remission annually, and the main mechanism of the decreased efficacy is assumed to be due to decreasing blood levels of the anti‐TNF‐α agent coupled with the formation of antidrug antibodies .…”

“…Treatment with anti-TNF-α agents, however, may cause difficulties, such as primary nonresponse, secondary loss of response (LOR) after achieving remission, and related adverse events, including paradoxical psoriasis. [4][5][6][7] LOR occurs in ~20% of CD patients treated with anti-TNF-α agents who achieved remission annually, and the main mechanism of the decreased efficacy is assumed to be due to decreasing blood levels of the anti-TNF-α agent coupled with the formation of antidrug antibodies. [7][8][9][10] The SONIC study (The Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease) and following studies demonstrated that combination therapy with IFX (chimeric IgG1 monoclonal antibody) and an immunomodulator effectively prevents LOR, and the pharmacokinetic data regarding their combination were better than for IFX monotherapy.…”

A Retrospective Claims Database Study on Drug Utilization in Japanese Patients with Crohn’s Disease Treated with Adalimumab or Infliximab

“…Clinical trials have demonstrated the efficacy and safety of ADA and IFX in the induction and maintenance of remission in patients with moderate to severe CD, in particular in Japanese patients [7, 8, 11–13]. However, treatment outcomes in the real-world setting might differ from clinical trials, as patients’ profiles may be more diverse and patients may not strictly adhere to a regular injection schedule.…”